title: Perioperative statin therapy for improving outcomes during and after noncardiac vascular surgery.
abstract: BACKGROUND
  Patients undergoing vascular surgery are a high-risk population with widespread atherosclerosis, an adverse cardiovascular risk profile and often multiple co-morbidities. Postoperative cardiovascular complications, including myocardial infarct (MI), are common. Statins are the medical treatment of choice to reduce high cholesterol levels. Evidence is accumulating that patients taking statins at the time of surgery are protected against a range of perioperative complications, but the specific benefits for patients undergoing noncardiac vascular surgery are not clear.
  
  
  OBJECTIVE
  We examined whether short-term statin therapy, commenced before or on the day of noncardiac vascular surgery and continuing for at least 48 hours afterwards, improves patient outcomes including the risk of complications, pain, quality of life and length of hospital stay. We also examined whether the effect of statin therapy on these outcomes changes depending on the dose of statin received.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE via Ovid SP (1966 to August 2012), EMBASE via Ovid SP (1966 to August 2012), CINAHL via EBSCO host (1966 to August 2012) and ISI Web of Science (1946 to July 2012) without any language restriction. We used a combination of free text search and controlled vocabulary search. The results were limited to randomized controlled clinical trials (RCTs). We conducted forwards and backwards citation of key articles and searched two clinical trial Websites for ongoing trials (www.clinicaltrials.gov and http://www.controlled-trials.com).
  
  
  METHODS
  We included RCTs that had compared short-term statin therapy, either commenced de novo or with existing users randomly assigned to different dosages, in adult participants undergoing elective and emergency noncardiac arterial surgery, including both open and endovascular procedures. We defined short-term as commencing before or on the day of surgery and continuing for at least 48 hours afterwards.
  
  
  METHODS
  Two authors independently assessed trial quality and extracted data, including information on adverse events. We contacted study authors for additional information. We performed separate analyses for the comparisons of statin with placebo/no treatment and between different doses of statin. We presented results as pooled risk ratios (RRs) with 95% confidence intervals (CIs) based on random-effects models (inverse variance method). We employed the Chi(2) test and calculated the I(2) statistic to investigate study heterogeneity.
  
  
  RESULTS
  We identified six eligible studies in total. The six Included studies were generally of high quality, but the largest eligible study was excluded because of concerns about its validity. Study populations were statin naive, which led to a considerable loss of eligible participants.Five RCTs compared statin use with placebo or standard care. We pooled results from three studies, with a total of 178 participants, for mortality and non-fatal event outcomes. In the statin group, 7/105 (6.7%) participants died within 30 days of surgery, as did 10/73 (13.7%) participants in the control group. Only one death in each group was from cardiovascular causes, with an incidence of 0.95% in statin participants and 1.4% in control participants, respectively. All deaths occurred in a single study population, and so effect estimates were derived from one study only. The risk ratio (RR) of all-cause mortality in statin users showed a non-significant decrease in risk (RR 0.73, 95% CI 0.31 to 1.75). For cardiovascular death, the risk ratio was 1.05 (95% CI 0.07 to 16.20). Non-fatal MI within 30 days of surgery was reported in three studies and occurred in 4/105 (3.8%) participants in the statin group and 8/73 (11.0%) participants receiving placebo, for a non-significant decrease in risk (RR 0.47, 95% CI 0.15 to 1.52). Several studies reported muscle enzyme levels as safety measures, but only three (with a total of 188 participants) reported explicitly on clinical muscle syndromes, with seven events reported and no significant difference found between statin users and controls (RR 0.94, 95% CI 0.24 to 3.63). The only participant-reported outcome was nausea in one small study,with no significant difference in risk between groups.Two studies compared different doses of atorvastatin, with a total of 145 participants, but reported data were not sufficient to allow us to determine the effect of higher doses on any outcome.
  
  
  CONCLUSIONS
  Evidence was insufficient to allow review authors to conclude that statin use resulted in either a reduction or an increase in any of the outcomes examined. The existing body of evidence leaves questions about the benefits of perioperative use of statins for vascular surgery unanswered. Widespread use of statins in the target population means that it may now be difficult for researchers to undertake the large RCTs needed to demonstrate any effect on the incidence of postoperative cardiovascular events. However, participant-reported outcomes have been neglected and warrant further study.
authors.affiliation: Surgical Outcomes Research Centre & Department of Anaesthesia, University College London Hospital & Wellcome Departmentof Imaging Neuroscience, University College London, London, UK.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sanders
authors.forename: Amanda
authors.initials: A
authors.lastname: Nicholson
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewis
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Smith
authors.forename: Phil
authors.initials: P
authors.lastname: Alderson
mesh_terms: D000328:Adult; D017130:Angioplasty; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy*; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D002423:Cause of Death; D002792:Cholestyramine Resin / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008148:Lovastatin / Q000627:therapeutic use; D019990:Perioperative Care / Q000379:methods; D011183:Postoperative Complications / Q000401:mortality / Q000517:prevention & control*; D011758:Pyrroles / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012855:Sitosterols / Q000627:therapeutic use; D014656:Vascular Surgical Procedures / Q000009:adverse effects* / Q000401:mortality
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D012855:Sitosterols; D002792:Cholestyramine Resin; C025473:gamma-sitosterol; D008148:Lovastatin; D000069059:Atorvastatin